Resumen

Este es un ensayo de fase 3 multicéntrico, aleatorizado, doble ciego y controlado de cabozantinib en combinación con nivolumab e ipilimumab frente a nivolumab e ipilimumab en combinación con placebo equivalente. Aproximadamente 840 sujetos elegibles con carcinoma de células renales (CCR) avanzado o metastásico de riesgo intermedio o desfavorable según los criterios del IMDC serán aleatorizados en una proporción 1:1 en aproximadamente 180 centros.

Descripción detallada

Este es un ensayo de fase 3 multicéntrico, aleatorizado, doble ciego y controlado de cabozantinib en combinación con nivolumab e ipilimumab frente a nivolumab e ipilimumab en combinación con placebo equivalente. El objetivo primario de este estudio es evaluar el efecto de cabozantinib en combinación con nivolumab e ipilimumab ("triplete") sobre la duración de la supervivencia libre de progresión (SLP) frente a nivolumab e ipilimumab. Un objetivo secundario es evaluar el efecto de la combinación en triplete sobre la duración de la supervivencia global (SG).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component.
Intermediate- or poor-risk RCC as defined by International Metastatic RCC Database Consortium (IMDC) criteria.
Measurable disease per RECIST 1.1 as determined by the Investigator. Measurable disease must be outside the radiation field if radiation therapy was previously administered.
Karnofsky Performance Status (KPS) ≥ 70%.
Adequate organ and marrow function.

Criterios de exclusión

Prior systemic anticancer therapy for unresectable locally advanced or metastatic RCC including investigational agents.
Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and stable for at least 4 weeks prior to randomization.
Concomitant anticoagulation with oral anticoagulants or platelet inhibitors.
Administration of a live, attenuated vaccine within 30 days prior to randomization.
Uncontrolled, significant intercurrent or recent illness including, but not limited to serious cardiovascular disorders (including uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment), GI disorders associated with high risk for perforation or fistula formation, tumors invading GI tract, bowel obstruction, intra-abdominal abscess, clinically significant bleeding events, cavitating pulmonary lesions, or lesions invading major pulmonary blood vessels.
Other clinically significant disorders such as:
Autoimmune disease that has been symptomatic or required treatment within the past two years from the date of randomization.
Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization.
Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active myobacterial infection.
Known history of COVID-19 unless the subject has clinically recovered from the disease at least 30 days prior to randomization.
Major surgery (eg, nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Minor surgeries within 10 days prior to randomization. Subjects must have complete wound healing from major or minor surgery before randomization.
Any other active malignancy at time of randomization or diagnosis of another malignancy within 3 years prior to randomization that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

Ubicaciones

Exelixis Clinical Site #153

Pilar, Buenos Aires, Argentina

Exelixis Clinical Site #109

Rosario, Santa Fe Province, Argentina

Exelixis Clinical Site #73

San Miguel de Tucumán, Tucumán Province, Argentina

Exelixis Clinical Site #54

Buenos Aires, Argentina

Exelixis Clinical Site #63

CABA, Argentina

Exelixis Clinical Site #110

Ciudad Autonoma de Buenos Aire, Argentina

Exelixis Clinical Site #120

Córdoba, Argentina

Estudio de fase 3, aleatorizado, doble ciego, controlado, de cabozantinib en combinación con nivolumab e ipilimumab frente a nivolumab e ipilimumab en sujetos con carcinoma de células renales avanzado o metastásico de riesgo intermedio o desfavorable no tratado previamente

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Cabozantinib

Nivolumab

Ipilimumab

Cabozantinib-matched placebo